The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors
Open accessAbstract
BACKGROUND: Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors. METHODS: We performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed. RESULTS: Among 21 tumor samples, 13 had RAS mutations (12 in HRAS). In a validation set of 14 samples, 8 had RAS mutations (4 in HRAS). Thus, 60% (21 of 35) of the specimens harbored RAS mutations, the most prevalent being HRAS Q61L. Increased proliferation of HRAS Q61L-mutant cell lines exposed to vemurafenib was associated with mitogen-activated protein kinase (MAPK)-pathway signaling and activation of ERK-mediated transcription. In a mouse model of HRAS Q61L-mediated skin carcinogenesis, the vemurafenib analogue PLX4720 was not an initiator or a promoter of carcinogenesis but accelerated growth of the lesions harboring HRAS mutations, and this growth was blocked by concomitant treatment with a MEK inhibitor. CONCLUSIONS: Mutations in RAS, particularly HRAS, are frequent in cutaneous squamous-cell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib. The molecular mechanism is consistent with the paradoxical activation of MAPK signaling and leads to accelerated growth of these lesions. (Funded by Hoffmann-La Roche and others; ClinicalTrials.gov numbers, NCT00405587, NCT00949702, NCT01001299, and NCT01006980.).
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Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
Self-citationImproved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720
Self-citationRAS oncogenes: the first 30 years
Malumbres, M., & Barbacid, M. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1097 · Cited by 1,902
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482
Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas
Balmain, A., Ramsden, M., Bowden, G. T., & Smith, J. (1984) · Nature · doi:10.1038/307658a0 · Cited by 529
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Self-citationDrugging the undruggable RAS: Mission Possible?
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Metadata
- Authors
- Su, F., Viros, A., Milagre, C., Trunzer, K., Bollag, G., Spleiss, O., Reis-Filho, J. S., Kong, X., Koya, R. C., Flaherty, K. T., Chapman, P. B., Kim, M. J., Hayward, R., Martin, M., Yang, H., Wang, Q., Hilton, H., Hang, J. S., Noe, J., Lambros, M., Geyer, F., Dhomen, N., Niculescu-Duvaz, I., Zambon, A., Niculescu-Duvaz, D., Preece, N., Robert, L., Otte, N. J., Mok, S., Kee, D., Ma, Y., Zhang, C., Habets, G., Burton, E. A., Wong, B., Nguyen, H., Kockx, M., Andries, L., Lestini, B., Nolop, K. B., Lee, R. J., Joe, A. K., Troy, J. L., Gonzalez, R., Hutson, T. E., Puzanov, I., Chmielowski, B., Springer, C. J., McArthur, G. A., Sosman, J. A., Lo, R. S., Ribas, A., & Marais, R.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-01-19
- Volume
- 366
- Issue
- 3
- Pages
- 207-215
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2155461614
- Cited by
- 1,038
- References
- 5
- FWCI
- 58.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Su, F., Viros, A., Milagre, C., Trunzer, K., Bollag, G., Spleiss, O., Reis-Filho, J. S., Kong, X., Koya, R. C., Flaherty, K. T., Chapman, P. B., Kim, M. J., Hayward, R., Martin, M., Yang, H., Wang, Q., Hilton, H., Hang, J. S., Noe, J., . . . Marais, R. (2012). RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1105358
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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